We will characterize the secretion of insulin-like growth factors, IGF I and IGF II, their binding by serum proteins and their reactions with specific receptors during both normal growth and development, and in a variety of relevant patholigical states. We have already identified an entire group of individuals with an isolated deficiency of IGF I, a previously unknown cause of growth retardation in man. By combining data on IGF and its carrier state with that obtained on growth hormone (GH) secretion, we will make a major advance in redefining the causes of growth retardation. More specificially, the entire classification of sexual ateliotic dwarfism will be reconstructed utilizing data on specific growth factors. This will provide for both a superior understanding and a more rationale approach to therapy of growth problems. The effect of starvation, diet composition and important hormones (estrogen, testosterone, growth hormone and human placental lactogen) on IGF secretion and IGF binding by serum protein will be examined in vivo and in vitro. In vitro studies will involve at least three specific tissues, one capable of producing IGF I and II (the isolated hepatocyte) another (dermal fibroblast) producing IGF I only. The relationship of IGF to the complications of diabetes will be investigated. We have made noteworthy contributions to this field for over 10 years. Our current preliminary data (the only available) indicate decreased IGF binding by serum proteins in diabetic subjects -- a possible important "link" in understanding the relationship of growth hormone to the complications of this disease. The ability to obtain our objectives by specific assays for IGF I and IFG II represents a major developmental advance for our laboratory. To the Senior Investigator's knowledge, there is no single laboratory in the United States with a comparable capacity.